Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas


Vasmatzis G., Johnson S. H. , Knudson R. A. , Ketterling R. P. , Braggio E., Fonseca R., ...Daha Fazla

BLOOD, cilt.120, ss.2280-2289, 2012 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 120 Konu: 11
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1182/blood-2012-03-419937
  • Dergi Adı: BLOOD
  • Sayfa Sayıları: ss.2280-2289

Özet

Peripheral T-cell lymphomas (PTCLs) are aggressive malignancies of mature T lymphocytes with 5-year overall survival rates of only similar to 35%. Improvement in outcomes has been stymied by poor understanding of the genetics and molecular pathogenesis of PTCL, with a resulting paucity of molecular targets for therapy. We developed bioinformatic tools to identify chromosomal rearrangements using genome-wide, next-generation sequencing analysis of mate-pair DNA libraries and applied these tools to 16 PTCL patient tissue samples and 6 PTCL cell lines. Thirteen recurrent abnormalities were identified, of which 5 involved p53-related genes (TP53, TP63, CDKN2A, WWOX, and ANKRD11). Among these abnormalities were novel TP63 rearrangements encoding fusion proteins homologous to Delta Np63, a dominant-negative p63 isoform that inhibits the p53 pathway. TP63 rearrangements were seen in 11 (5.8%) of 190 PTCLs and were associated with inferior overall survival; they also were detected in 2 (1.2%) of 164 diffuse large B-cell lymphomas. As TP53 mutations are rare in PTCL compared with other malignancies, our findings suggest that a constellation of alternate genetic abnormalities may contribute to disruption of p53-associated tumor suppressor function in PTCL. (Blood. 2012;120(11):2280-2289)